GENETICS OF ALLERGY · Characterization of the genetic basis of Atopic Dermatitis
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2008-03-01 → 2010-02-28
- EU contribution
- €158,197
- Participants
- 1
- Scheme
- EIF
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Results in brief
Final Activity Report Summary - GENETICS OF ALLERGY (Characterization of the genetic basis of Atopic Dermatitis.)
We successfully performed the first genome-wide association study for atopic dermatitis reported to date. This study included 10 000 individuals and provided strong evidence for a new susceptibility locus for eczema on chromosome 11q13.5 (P = 7.6 x 10-10). Homozygous carriers of the risk allele rs7927894[A] represented 11 % of the population and their risk of developing eczema was 1.47 times higher than in non-carriers. Our study also detected association with the epidermal differentiation complex in 1q21. The loss-of-function mutations in the filaggrin gene, which was located in this gene cluster, were the best replicated atopic dermatitis susceptibility factor to date. Importantly, our data suggested that, apart from filaggrin mutations, additional risk factors existed in this extremely interesting cluster of genes involved in skin differentiation. These results were published in Nature Genetics in 2009. We also isolated peripheral blood mononuclear cells (PBMCs) from 210 individuals and generated genome-wide ribonucleic acid (mRNA) expression and single nucleotide polymorphism (SNP) data in order to detect the genetic factors determining the gene expression levels. We finally used this data set to identify genetic markers which increased disease risk and additionally affected gene expression levels.
Data: CORDIS, © European Union
Project objective
Atopic Dermatitis (AD, also known as eczema) is a chronic inflammatory skin disease affecting 10-20% of children in western societies. AD is a complex disease arising from the interaction between genetic and environmental factors.Various genome-wide linkage scans have been undertaken to search for AD susceptibility genes with potential sites identified at various chromosomal locations. However, very little is known about AD causatives genes.The aim of this project will be the identification of the genetic determinants of AD through genome-wide association. The Affymetrix GeneChip® Mapping 500K Set will be used for the analysis of more than 500.000 Single Nucleotide Polymorphisms (SNPs) on each individual.The sample will consist of 250 nuclear families (10 00 individuals) selected on the basis of siblings with early onset AD and high/moderate disease severity. Statistical analyses of the acquired data will allow the determination of the SNPs associated to AD and will permit the characterisation of novel AD susceptibility genes.Additionally, the Affymetrix Human Genome U133 Set GeneChip array will be used to perform a gene expression analysis in T lymphocytes in a subset of 50 AD families. Gene expression profiling will enable the study of correlations between mRNA levels and disease status and severity.Since the SNPs genotypes will be available, linkage and association analysis will be performed in order to identify the genes regulating the mRNA expression levels and their potential relation with AD.The present project will enable the applicant to acquire expertise in state of the art tools for complex disease mapping, including high throughput genotyping and statistical genetics. Moreover, this will be achieved in a multidisciplinary setting where biotechnology and functional genomics meet clinical research.The fellowship will help the applicant to pursue his goal to become an independent and leading scientist in complex disease gene mapping.
Original text from CORDIS.
Participants
- CHARITE UNIVERSITäTSMEDIZIN BERLIN · BERLINCoordinatorCity levelGermany
Links
Data: CORDIS, © European Union